神经免疫文献阅读第4期：Immunity—小胶质细胞研究重磅突破：疾病相关小胶质细胞（DAM）分为两个功能不同的亚群

中文摘要

脑巨噬细胞群包括实质小胶质细胞、边界相关巨噬细胞和招募的单核细胞衍生细胞，它们共同控制大脑发育和稳态，但也与衰老和神经变性的发病机制有关。目前，上述3个细胞群体在不同背景下的表型、定位和功能尚未被解析。科学家生成了一个小鼠大脑髓系scRNA-seq整合数据集，以系统地描绘脑巨噬细胞群体。科学家发现，在小鼠阿尔茨海默病模型中检测到的先前确定的疾病相关小胶质细胞（DAM）群体实际上包括两个分子特征和功能上不同的细胞谱系：TREM2依赖的表达神经保护标记的DAM和在衰老大脑中聚集的单核细胞衍生的表达TREM2的疾病炎症巨噬细胞（DIMs）。这两个不同的群体似乎在人类大脑中也是保守的。在此，科学家建立了发育、稳态和疾病等条件下脑巨噬细胞异质性的发育解析模型，并确定了治疗神经变性疾病的细胞靶点。

英文摘要

Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations. We show that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer's disease models actually comprises two ontogenetically and functionally distinct cell lineages: embryonically derived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressing a neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatory macrophages (DIMs) accumulating in the brain during aging. These two distinct populations appear to also be conserved in the human brain. Herein, we generate an ontogeny-resolved model of brain myeloid cell heterogeneity in development, homeostasis, and disease and identify cellular targets for the treatment of neurodegeneration.

参考文献：Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration.Immunity. 2022 Aug 9;55(8):1448-1465.e6. doi: 10.1016/j.immuni.2022.07.004. Epub 2022 Aug 4.